tbuckley/cabot-search huggingface dataset:
RETRACTED: Dynamic Prediction of Outcomes for Youth at Clinical High Risk for Psychosis
Authors: Michelle A. Worthington, Jean Addington, Carrie E. Bearden, Kristin S. Cadenhead, Barbara A. Cornblatt, Matcheri Keshavan, Cole A. Lympus, Daniel H. Mathalon, Diana O. Perkins, William S. Stone, Elaine F. Walker, Scott W. Woods, Yize Zhao, Tyrone D. Cannon
Journal: JAMA Psychiatry (2023)

Importance Leveraging the dynamic nature of clinical variables in the clinical high risk for psychosis (CHR-P) population has the potential to significantly improve the performance of outcome prediction models. Objective To improve performance of prediction models and elucidate dynamic clinical profiles using joint modeling to predict conversion to psychosis and symptom remission. Design, Setting, and Participants Data were collected as part of the third wave of the North American Prodrome Longitudinal Study (NAPLS 3), which is a 9-site prospective longitudinal study. Participants were individuals aged 12 to 30 years who met criteria for a psychosis-risk syndrome. Clinical, neurocognitive, and demographic variables were collected at baseline and at multiple follow-up visits, beginning at 2 months and up to 24 months. An initial feature selection process identified longitudinal clinical variables that showed differential change for each outcome group across 2 months. With these variables, a joint modeling framework was used to estimate the likelihood of eventual outcomes. Models were developed and tested in a 10-fold cross-validation framework. Clinical data were collected between February 2015 and November 2018, and data were analyzed from February 2022 to December 2023. Main Outcomes and Measures Prediction models were built to predict conversion to psychosis and symptom remission. Participants met criteria for conversion if their positive symptoms reached the fully psychotic range and for symptom remission if they were subprodromal on the Scale of Psychosis-Risk Symptoms for a duration of 6 months or more. Results Of 488 included NAPLS 3 participants, 232 (47.5%) were female, and the mean (SD) age was 18.2 (3.4) years. Joint models achieved a high level of accuracy in predicting conversion (balanced accuracy [BAC], 0.91) and remission (BAC, 0.99) compared with baseline models (conversion: BAC, 0.65; remission: BAC, 0.60). Clinical variables that showed differential change between outcome groups across a 2-month span, including measures of symptom severity and aspects of functioning, were also identified. Further, intra-individual risks for each outcome were more negatively correlated when using joint models ( r = −0.92; P &amp;amp;lt; .001) compared with baseline models ( r = −0.50; P &amp;amp;lt; .001). Conclusions and Relevance In this study, joint models significantly outperformed baseline models in predicting both conversion and remission, demonstrating that monitoring short-term clinical change may help to parse heterogeneous dynamic clinical trajectories in a CHR-P population. These findings could inform additional study of targeted treatment selection and could move the field closer to clinical implementation of prediction models.
Mechanisms of gut epithelial barrier impairment caused by food emulsifiers polysorbate 20 and polysorbate 80
Authors: Ismail Ogulur, Duygu Yazici, Yagiz Pat, Elif Naz Bingöl, Huseyn Babayev, Sena Ardicli, Anja Heider, Beate Rückert, Vanitha Sampath, Raja Dhir, Mubeccel Akdis, Kari Nadeau, Cezmi A. Akdis
Journal: Allergy (2023)

The rising prevalence of many chronic diseases related to gut barrier dysfunction coincides with the increased global usage of dietary emulsifiers in recent decades. We therefore investigated the effect of the frequently used food emulsifiers on cytotoxicity, barrier function, transcriptome alterations, and protein expression in gastrointestinal epithelial cells.Human intestinal organoids originating from induced pluripotent stem cells, colon organoid organ-on-a-chip, and liquid-liquid interface cells were cultured in the presence of two common emulsifiers: polysorbate 20 (P20) and polysorbate 80 (P80). The cytotoxicity, transepithelial electrical resistance (TEER), and paracellular-flux were measured. Immunofluorescence staining of epithelial tight-junctions (TJ), RNA-seq transcriptome, and targeted proteomics were performed.Cells showed lysis in response to P20 and P80 exposure starting at a 0.1% (v/v) concentration across all models. Epithelial barrier disruption correlated with decreased TEER, increased paracellular-flux and irregular TJ immunostaining. RNA-seq and targeted proteomics analyses demonstrated upregulation of cell development, signaling, proliferation, apoptosis, inflammatory response, and response to stress at 0.05%, a concentration lower than direct cell toxicity. A proinflammatory response was characterized by the secretion of several cytokines and chemokines, interaction with their receptors, and PI3K-Akt and MAPK signaling pathways. CXCL5, CXCL10, and VEGFA were upregulated in response to P20 and CXCL1, CXCL8 (IL-8), CXCL10, LIF in response to P80.The present study provides direct evidence on the detrimental effects of food emulsifiers P20 and P80 on intestinal epithelial integrity. The underlying mechanism of epithelial barrier disruption was cell death at concentrations between 1% and 0.1%. Even at concentrations lower than 0.1%, these polysorbates induced a proinflammatory response suggesting a detrimental effect on gastrointestinal health.
Evaluation of Field Sobriety Tests for Identifying Drivers Under the Influence of Cannabis
Authors: Thomas D. Marcotte, Anya Umlauf, David J. Grelotti, Emily G. Sones, Kyle F. Mastropietro, Raymond T. Suhandynata, Marilyn A. Huestis, Igor Grant, Robert L. Fitzgerald
Journal: JAMA Psychiatry (2023)

With increasing medicinal and recreational cannabis legalization, there is a public health need for effective and unbiased evaluations for determining whether a driver is impaired due to Δ9-tetrahydrocannabinol (THC) exposure. Field sobriety tests (FSTs) are a key component of the gold standard law enforcement officer-based evaluations, yet controlled studies are inconclusive regarding their efficacy in detecting whether a person is under the influence of THC.
Intraoperative Identification of Thyroid and Parathyroid Tissues During Human Endocrine Surgery Using the MasSpec Pen
Authors: Rachel J. DeHoog, Mary E. King, Michael F. Keating, Jialing Zhang, Marta Sans, Clara L. Feider, Kyana Y. Garza, Alena Bensussan, Anna Krieger, John Q. Lin, Sunil Badal, Elizabeth Alore, Christopher Pirko, Kirtan Brahmbhatt, Wendong Yu, Raymon Grogan, Livia S. Eberlin, James Suliburk
Journal: JAMA Surgery (2023)

Intraoperative identification of tissues through gross inspection during thyroid and parathyroid surgery is challenging yet essential for preserving healthy tissue and improving outcomes for patients.
<scp>Anti‐Gephyrin</scp> Antibodies: A Novel Specificity in Patients With Systemic Sclerosis and Lower Bowel Dysfunction
Authors: Zsuzsanna H. McMahan, Subhash Kulkarni, Felipe Andrade, Jamie Perin, Chengxiu Zhang, Jody E. Hooper, Fredrick M. Wigley, Antony Rosen, Pankaj J. Pasricha, Livia Casciola‐Rosen
Journal: Arthritis & Rheumatology (2023)

Autoantibodies are clinically useful in phenotyping patients with systemic sclerosis (SSc). Gastrointestinal (GI) function is regulated by the enteric nervous system (ENS) and commonly impaired in SSc, suggesting that the SSc autoimmune response may target ENS antigens. We sought to identify novel anti-ENS autoantibodies with an aim to clinically phenotype SSc GI dysfunction.
Differences in Use of Clinical Decision Support Tools and Implementation of Aspirin, Blood Pressure Control, Cholesterol Management, and Smoking Cessation Quality Metrics in Small Practices by Race and Sex
Authors: Madeline M. Roberts, Miguel Marino, Rebecca Wells, Folefac D. Atem, Bijal A. Balasubramanian
Journal: JAMA Network Open (2023)

Practice-level evidence is needed to clarify the value of population-based clinical decision support (CDS) tools in reducing racial and sex disparities in cardiovascular care.To evaluate the association between CDS tools and racial and sex disparities in the aspirin use, blood pressure control, cholesterol management, and smoking cessation (ABCS) care quality metrics among smaller primary care practices.This cross-sectional study used practice-level data from the Agency for Healthcare Research and Quality-funded EvidenceNOW initiative. The national initiative from May 1, 2015, to April 30, 2021, spanned 12 US states and focused on improving cardiovascular preventive care by providing quality improvement support to smaller primary care practices. A total of 576 primary care practices in EvidenceNOW submitted both survey data and electronic health record (EHR)-derived ABCS data stratified by race and sex.Practice-level estimates of disparities between Black and White patients and between male and female patients were calculated as the difference in proportions of eligible patients within each practice meeting ABCS care quality metrics. The association between CDS tools (EHR prompts, standing orders, and clinical registries) and disparities was evaluated by multiply imputed multivariable models for each CDS tool, adjusted for practice rurality, ownership, and size.Across the 576 practices included in the analysis, 219 (38.0%) had patient panels that were more than half White and 327 (56.8%) had panels that were more than half women. The proportion of White compared with Black patients meeting metrics for blood pressure (difference, 5.16% [95% CI, 4.29%-6.02%]; P < .001) and cholesterol management (difference, 1.49% [95% CI, 0.04%-2.93%] P = .04) was higher; the proportion of men meeting metrics for aspirin use (difference, 4.36% [95% CI, 3.34%-5.38%]; P < .001) and cholesterol management (difference, 3.88% [95% CI, 3.14%-4.63%]; P < .001) was higher compared with women. Conversely, the proportion of women meeting practice blood pressure control (difference, -1.80% [95% CI, -2.32% to -1.28%]; P < .001) and smoking cessation counseling (difference, -1.67% [95% CI, -2.38% to -0.95%]; P < .001) metrics was higher compared with men. Use of CDS tools was not associated with differences in race or sex disparities except for the smoking metric. Practices using CDS tools showed a higher proportion of men meeting the smoking counseling metric than women (coefficient, 3.82 [95% CI, 0.95-6.68]; P = .009).The findings of this cross-sectional study suggest that practices using CDS tools had small disparities that were not statistically significant, but CDS tools were not associated with reductions in disparities. More research is needed on effective practice-level interventions to mitigate disparities.
Citizen science helps to raise awareness about gut microbiome health in people at risk of developing non-communicable diseases
Authors: Silvia Garcia, Sheyla Ordoñez, Victor Manuel López-Molina, Blanca Lacruz-Pleguezuelos, Enrique Carrillo de Santa Pau, Laura Judith Marcos-Zambrano
Journal: Gut Microbes (2023)

Citizens lack knowledge about the impact of gut microbiota on health and how lifestyle and dietary choices can influence it, leading to Non-Communicable Diseases (NCDs) and affecting overall well-being. Participatory action research (PAR) is a promising approach to enhance communication and encourage individuals to adopt healthier behaviors and improve their health. In this study, we explored the feasibility of integrating the photovoice method with citizen science approaches to assess the impact of social and environmental factors on gut microbiota health. In this context, citizen science approaches entailed the involvement of participants in the collection of samples for subsequent analysis, specifically gut microbiome assessment via 16S rRNA gene sequencing. We recruited 70 volunteers and organized six photovoice groups based on age and educational background. Participants selected 64 photographs that represented the influence of daily habits on gut microbiota health and created four photovoice themes. Analysis of the gut microbiome using 16S rRNA gene sequencing identified 474 taxa, and in-depth microbial analysis revealed three clusters of people based on gut microbiome diversity and body mass index (BMI). Our findings indicate that participants enhanced their knowledge of gut microbiome health through PAR activities, and we found a correlation between lower microbial diversity, higher BMI, and better achievement of learning outcomes. Using PAR as a methodology is an effective way to increase citizens' awareness and engagement in self-care, maintain healthy gut microbiota, and prevent NCD development. These interventions are particularly beneficial for individuals at higher risk of developing NCDs.
Ketamine Infusions for Treatment-Resistant Neuropathic Pruritus
Authors: Shawn G. Kwatra, Anusha Kambala, Hannah Cornman, Sriya V. Reddy, Steven P. Cohen
Journal: JAMA Dermatology (2023)

This case report describes a patient in her 50s with a 4-year history of brachioradial pruritus with bilateral pruritus on her upper arms and forearms.
Revisiting the Use of Antibiotics to Prevent COPD Exacerbation: Is Doxycycline the Answer?
Authors: Muhammad Adrish, Nicola A. Hanania
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Revisiting the Use of Antibiotics to Prevent COPD Exacerbation: Is Doxycycline the Answer?." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Homoharringtonine-Based Induction Regimen Improved the Remission Rate and Survival Rate in Chinese Childhood AML: A Report From the CCLG-AML 2015 Protocol Study
Authors: Jing Li, Ju Gao, Ansheng Liu, Wei Liu, Hao Xiong, Changda Liang, Yongjun Fang, Yunpeng Dai, Jingbo Shao, Hui Yu, Lingzhen Wang, Li Wang, Liangchun Yang, Mei Yan, Xiaowen Zhai, Xiaodong Shi, Xin Tian, Xiuli Ju, Yan Chen, Jing Wang, Leping Zhang, Hui Liang, Sen Chen, Jingrong Zhang, Haixia Cao, Jiao Jin, Qun Hu, Junlan Wang, Yilin Wang, Min Zhou, Yueqin Han, Rong Zhang, Weihong Zhao, Xiaoli Wang, Limin Lin, Ruidong Zhang, Chao Gao, Liting Xu, Yuanyuan Zhang, Jia Fan, Ying Wu, Wei Lin, Jiaole Yu, Peijing Qi, Pengli Huang, Xiaoxia Peng, Yaguang Peng, Tianyou Wang, Huyong Zheng
Journal: Journal of Clinical Oncology (2023)

PURPOSE Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm ( P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm ( P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.
Gut-licensed β7 <sup>+</sup> CD4 <sup>+</sup> T cells contribute to progressive retinal ganglion cell damage in glaucoma
Authors: Chong He, Wenbo Xiu, Qinyuan Chen, Kun Peng, Xiong Zhu, Zuo Wang, Xiang Xu, Yang Chen, Gao Zhang, Jing Fu, Qiwei Dong, Xiaoqiong Wu, An Li, Donghua Liu, Yanping Gao, Jinxia Wang, Zhao Wang, Bolin Deng, Ping Shuai, Caiping Gao, Yilian Chen, Ling Yu, Fang Lu
Journal: Science Translational Medicine (2023)

Glaucoma is the leading cause of irreversible blindness. Currently, most therapeutic strategies aim to reduce elevated intraocular pressure (EIOP), but this does not always halt disease progression. Evidence suggests a role for T cells in glaucoma pathogenesis, but the underlying mechanisms remain largely unknown. Here, we found that the percentage of circulating CD4 + T cells expressing a gut-homing integrin β7 was increased in patients with glaucoma and was associated with disease stage. In an EIOP-triggered glaucoma mouse model, β7 + CD4 + T cells infiltrated the retina in the progressive phase of glaucoma via eliciting retinal endothelial cell expression of mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1). MAdCAM-1 was minimally detected in retinas of healthy mice, and neutralization with an MAdCAM-1 antibody ameliorated retinal ganglion cell (RGC) loss and glial activity in mice with glaucoma. We furthermore found that EIOP-induced β7 + CD4 + T cells homed to the gut during the acute phase of glaucoma, which was essential for progressive RGC damage in diseased mice. Gut-homing β7 + CD4 + T cells underwent transcriptional reprogramming, showing up-regulated pathways enriched in autoimmune diseases, bacteria responses, mucosal immunity, and glial activity. Gut-homing β7 + CD4 + T cells gained the competence to induce retinal MAdCAM-1 expression and to cross the blood-retina barrier. Together, our study reveals a role of gut-licensed β7 + CD4 + T cells and MAdCAM-1 in RGC degeneration and emphasizes the importance of the “gut-retina” axis in glaucoma.
Alternative splicing of CEACAM1 by hypoxia-inducible factor–1α enhances tolerance to hepatic ischemia in mice and humans
Authors: Kenneth J. Dery, Hidenobu Kojima, Shoichi Kageyama, Kentaro Kadono, Hirofumi Hirao, Brian Cheng, Yuan Zhai, Douglas G. Farmer, Fady M. Kaldas, Xiaoyi Yuan, Holger K. Eltzschig, Jerzy W. Kupiec-Weglinski
Journal: Science Translational Medicine (2023)

Although alternative splicing (AS) drives transcriptional responses and cellular adaptation to environmental stresses, its contributions in organ transplantation have not been appreciated. We have shown that carcinoembryonic antigen–related cell adhesion molecule (Ceacam1; CD66a ), a transmembrane biliary glycoprotein expressed in epithelial, endothelial, and immune cells, determines donor liver transplant quality. Here, we studied how AS of Ceacam1 affects ischemia-reperfusion injury (IRI) in mouse and human livers. We found that the short cytoplasmic isoform Ceacam1-S increased during early acute and late resolution phases of warm IRI injury in mice. Transfection of Ceacam1-deficient mouse hepatocytes with adenoviral Ceacam1-S mitigated hypoxia-induced loss of cellular adhesion by repressing the Ask1/p-p38 cell death pathway. Nucleic acid–blocking morpholinos, designed to selectively induce Ceacam1-S, protected hepatocyte cultures against temperature-induced stress in vitro. Luciferase and chromatin immunoprecipitation assays identified direct binding of hypoxia-inducible factor–1α (Hif-1α) to the mouse polypyrimidine tract binding protein 1 ( Ptbp1 ) promoter region. Dimethyloxalylglycine protected mouse livers from warm IR stress and hepatocellular damage by inhibiting prolyl hydroxylase domain–containing protein 1 and promoting AS of Ceacam1-S . Last, analysis of 46 human donor liver grafts revealed that CEACAM1-S positively correlated with pretransplant HIF1A expression. This also correlated with better transplant outcomes, including reduced TIMP1 , total bilirubin, proinflammatory MCP1 , CXCL10 cytokines, immune activation markers IL17A , and incidence of delayed complications from biliary anastomosis. This translational study identified mouse Hif-1α–controlled AS of Ceacam1 , through transcriptional regulation of Ptbp1 promoter region, as a functional underpinning of hepatoprotection against IR stress and tissue damage in liver transplantation.
Single-cell transcriptomics identifies prothymosin α restriction of HIV-1 in vivo
Authors: Aviva Geretz, Philip K. Ehrenberg, Robert J. Clifford, Alexandre Laliberté, Caterina Prelli Bozzo, Daina Eiser, Gautam Kundu, Lauren K. Yum, Richard Apps, Matthew Creegan, Mohamed Gunady, Shida Shangguan, Eric Sanders-Buell, Carlo Sacdalan, Nittaya Phanuphak, Sodsai Tovanabutra, Ronnie M. Russell, Frederic Bibollet-Ruche, Merlin L. Robb, Nelson L. Michael, Julie A. Ake, Sandhya Vasan, Denise C. Hsu, Beatrice H. Hahn, Frank Kirchhoff, Rasmi Thomas
Journal: Science Translational Medicine (2023)

Host restriction factors play key roles in innate antiviral defense, but it remains poorly understood which of them restricts HIV-1 in vivo. Here, we used single-cell transcriptomic analysis to identify host factors associated with HIV-1 control during acute infection by correlating host gene expression with viral RNA abundance within individual cells. Wide sequencing of cells from one participant with the highest plasma viral load revealed that intracellular viral RNA transcription correlates inversely with expression of the gene PTMA , which encodes prothymosin α. This association was genome-wide significant ( P adjusted &lt; 0.05) and was validated in 28 additional participants from Thailand and the Americas with HIV-1 CRF01_AE and subtype B infections, respectively. Overexpression of prothymosin α in vitro confirmed that this cellular factor inhibits HIV-1 transcription and infectious virus production. Our results identify prothymosin α as a host factor that restricts HIV-1 infection in vivo, which has implications for viral transmission and cure strategies.
Measuring translational research impact requires reaching beyond current metrics
Authors: Georg N. Duda, David W. Grainger, Robert E. Guldberg, Gady Goldsobel, Glenn D. Prestwich, Brenna Rauw, Hans-Dieter Volk
Journal: Science Translational Medicine (2023)

Translational impact assessment is key to selecting those biomedical research discoveries most likely to be converted into viable new products to improve human health. However, metrics for translational success are variable, are not limited to commercial success, and may not be relevant to every case or institution. Societal impact is a top translational priority in a globalized society.